Steven R. Barczi

Impaired Vascular Regulation in Patients with Obstructive Sleep Apnea: Effects of Continuous Positive Airway Pressure Treatment

RATIONALE Impaired endothelium-dependent vasodilation has been documented in patients with sleep apnea. This impairment may result in blood flow dysregulation during apnea-induced fluctuations in arterial blood gases. OBJECTIVES To test the hypothesis that hypoxic and hypercapnic vasodilation in the forearm and cerebral circulation are impaired in patients with sleep apnea. METHODS We exposed 20 patients with moderate to severe sleep apnea and 20 control subjects, to isocapnic hypoxia and hyperoxic hypercapnia. A subset of 14 patients was restudied after treatment with continuous positive airway pressure. MEASUREMENTS AND MAIN RESULTS Cerebral flow velocity (transcranial Doppler), forearm blood flow (venous occlusion plethysmography), arterial pressure (automated sphygmomanometry), oxygen saturation (pulse oximetry), ventilation (pneumotachograph), and end-tidal oxygen and carbon dioxide tensions (expired gas analysis) were measured during three levels of hypoxia and two levels of hypercapnia. Cerebral vasodilator responses to hypoxia (-0.65 +/- 0.44 vs. -1.02 +/- 0.72 [mean +/- SD] units/% saturation; P = 0.03) and hypercapnia (2.01 +/- 0.88 vs. 2.57 +/- 0.89 units/mm Hg; P = 0.03) were smaller in patients versus control subjects. Hypoxic vasodilation in the forearm was also attenuated (-0.05 +/- 0.09 vs. -0.10 +/- 0.09 unit/% saturation; P = 0.04). Hypercapnia did not elicit forearm vasodilation in either group. Twelve weeks of continuous positive airway pressure treatment enhanced hypoxic vasodilation in the cerebral circulation (-0.83 +/- 0.32 vs. -0.46 +/- 0.29 units/% saturation; P = 0.01) and forearm (-0.19 +/- 0.15 vs. -0.02 +/- 0.08 units/% saturation; P = 0.003), and hypercapnic vasodilation in the brain showed a trend toward improvement (2.24 +/- 0.78 vs. 1.76 +/- 0.64 units/mm Hg; P = 0.06). CONCLUSIONS Vasodilator responses to chemical stimuli in the cerebral circulation and the forearm are impaired in many patients with obstructive sleep apnea. Some of these impairments can be improved with continuous positive airway pressure.

Influence of cerebral blood flow on breathing stability

Our previous work showed a diminished cerebral blood flow (CBF) response to changes in Pa(CO(2)) in congestive heart failure patients with central sleep apnea compared with those without apnea. Since the regulation of CBF serves to minimize oscillations in H(+) and Pco(2) at the site of the central chemoreceptors, it may play an important role in maintaining breathing stability. We hypothesized that an attenuated cerebrovascular reactivity to changes in Pa(CO(2)) would narrow the difference between the eupneic Pa(CO(2)) and the apneic threshold Pa(CO(2)) (DeltaPa(CO(2))), known as the CO(2) reserve, thereby making the subjects more susceptible to apnea. Accordingly, in seven normal subjects, we used indomethacin (Indo; 100 mg by mouth) sufficient to reduce the CBF response to CO(2) by approximately 25% below control. The CO(2) reserve was estimated during non-rapid eye movement (NREM) sleep. The apnea threshold was determined, both with and without Indo, in NREM sleep, in a random order using a ventilator in pressure support mode to gradually reduce Pa(CO(2)) until apnea occurred. results: Indo significantly reduced the CO(2) reserve required to produce apnea from 6.3 +/- 0.5 to 4.4 +/- 0.7 mmHg (P = 0.01) and increased the slope of the ventilation decrease in response to hypocapnic inhibition below eupnea (control vs. Indo: 1.06 +/- 0.10 vs. 1.61 +/- 0.27 l x min(-1) x mmHg(-1), P < 0.05). We conclude that reductions in the normal cerebral vascular response to hypocapnia will increase the susceptibility to apneas and breathing instability during sleep.

Effects of estrogen replacement therapy on the circadian rhythms of serum cortisol and body temperature in postmenopausal women

Estrogen replacement therapy (ERT) seems to enhance longevity in women. Both gender and aging have been shown to influence the regulation of circadian rhythms, yet little is known about the effect of ERT on circadian regulation. The aim of this study was to determine the effects of ERT (oral conjugated estrogen: Premarin, 0.625 mg) for 6-8 weeks on circadian serum cortisol by continuous blood sampling every 15 min for 24 h with simultaneous measurements of body temperature in six healthy postmenopausal women (range, 54-61 years). The results are presented as median values (range in quartiles). The circadian amplitude of cortisol increased during ERT from 20.20 (18.35, 23.61) to 25.97 (24.94, 27.74) microg/dL (p = 0.016), whereas the timing of nocturnal nadir and morning acrophase did not differ significantly. ERT lowered the 24-h body temperature from 37.03 degrees C (36.95 degrees C, 37.07 degrees C) to 36.90 degrees C (36.77 degrees C, 36.97 degrees C) (p = 0.038), but did not alter the peak and trough body temperatures significantly. These findings are noteworthy because the increased circadian amplitude of serum cortisol during ERT contrasts with the reduction in circadian amplitude seen with normal aging. The reduction in body temperature confirms the regulatory effect of ERT in thermoregulation and has implications regarding the correlation between basal metabolic rate and life span.

Effects of Sleep Disordered Breathing on Cerebrovascular Regulation: A Population-Based Study

RATIONALE Cerebrovascular regulation is impaired in patients with moderate to severe obstructive sleep apnea; however, it is unknown whether this impairment exists in individuals with less severe sleep-disordered breathing. OBJECTIVES To test the hypothesis that cerebrovascular responses to hypercapnia are attenuated in a nonclinical population-based cohort. METHODS A rebreathing test that raised end-tidal CO₂ tension by 10 mm Hg was performed during wakefulness in 373 participants of the Wisconsin Sleep Cohort. MEASUREMENTS AND MAIN RESULTS We measured cerebral flow velocity (transcranial Doppler ultrasound); heart rate (electrocardiogram); blood pressure (photoplethysmograph); ventilation (pneumotachograph); and end-tidal CO₂ (expired gas analysis). Cerebrovascular CO₂ responsiveness was quantified as the slope of the linear relationship between flow velocity and end-tidal CO₂ during rebreathing. Linear regression analysis was performed using cerebrovascular CO₂ responsiveness as the outcome variable. Main independent variables were the apnea-hypopnea index and the mean level of arterial oxygen saturation during sleep. We observed a positive correlation between cerebrovascular CO₂ responsiveness and the mean level of oxygen saturation during sleep that was statistically significant in unadjusted analysis and after adjustment for known confounders and the increase in arterial pressure during rebreathing. Each 5% decrease in Sa(O₂) during sleep predicted a decrease in cerebrovascular reactivity of 0.4 ± 0.2 cm/second/mm Hg P(ET)CO₂. In contrast, the negative correlation between cerebrovascular CO₂ responsiveness and apnea-hypopnea index was statistically significant only in the unadjusted analysis. CONCLUSIONS Hypercapnic vasodilation in the cerebral circulation is blunted in individuals with sleep-disordered breathing. This impairment is correlated with hypoxemia during sleep.

A Multisite Geriatric Education Program for Rural Providers in the Veteran Health Care System (GRECC-Connect)

Older patients who live in rural areas often have limited access to specialty geriatric care, which can help in identifying and managing geriatric conditions associated with functional decline. Implementation of geriatric-focused practices among rural primary care providers has been limited, because rural providers often lack access to training in geriatrics and to geriatricians for consultation. To bridge this gap, four Geriatric Research, Education, and Clinical Centers, which are centers of excellence across the nation for geriatric care within the Veteran health system, have developed a program utilizing telemedicine to connect with rural providers to improve access to specialized geriatric interdisciplinary care. In addition, case-based education via teleconferencing using cases brought by rural providers was developed to complement the clinical implementation efforts. In this article, the authors review these educational approaches in the implementation of the clinical interventions and discuss the potential advantages in improving implementation efforts.

Veterans Affairs Geriatric Scholars Program: Enhancing Existing Primary Care Clinician Skills in Caring for Older Veterans

The Veterans Affairs Geriatric Scholars Program (GSP) is a continuing professional development program to integrate geriatrics into the clinical practices of primary care providers and select associated health professions that support primary care teams. GSP uses a blended program educational format, and the minimal requirements are to attend an intensive course in geriatrics, participate in an interactive workshop on quality improvement (QI), and initiate a local QI project to demonstrate application of new knowledge to benefit older veterans. Using a retrospective post/pre survey design, the effect of GSP on clinical practices and behaviors and variation of that effect on clinicians working in rural and nonrural settings were evaluated. Significant improvement was found in the frequency of using evidence‐based brief standardized assessments, clinical decision‐making, and standards of care. Significant subgroup differences were observed in peer‐to‐peer information sharing between rural and nonrural clinicians. Overall, 77% of the sample reported greater job satisfaction after participating in GSP. The program is a successful model for advancing postgraduate education in geriatrics and a model that might be replicated to increase access to quality health care, particularly in rural areas.